The present invention relates to a process for preparing bicyclic amine derivatives such 2-aminotetralines, 2-aminoindanes, 3-aminochromanes, 3-aminothiochromanes or 3-amino-1,2,3,4-tetrahydroquinolines by asymmetric hydrogenation of the corresponding enamines. The invention also relates to intermediates of said process.
Certain 1-substituted 2-aminotetraline and 2-aminoindanes and 4-substituted 3-aminochromane, 3-aminothiochromane and 3-amino-1,2,3,4-tetrahydroquinoline derivatives are of great interest as pharmaceutical agents or their synthetical precursors. Such derivatives have been described in WO 00/20376, for instance, as ligands for the neuropeptide Y receptor of subtype Y5, and in WO 2010/092180 and WO 2012/020131 as inhibitors of glycine transporter 1. However, for preparing these compounds in high chiral purity the aforementioned documents only disclose multi-step processes that require chiral separation of enantiomeric mixtures.
While the catalytic enantioselective hydrogenation of enamines is a known process, there are only few pior art reports on the asymmetric hydrogenation of cyclic enamines that have a tetrasubstituted double bound and an exocyclic amino group.
Ma et al., Tetrahedron: Asymmetry, 2011, 22, 506-511, describe rhodium-catalyzed asymmetric hydrogenations of 1-acetylamino-2-cyano-cyclopentene and -cyclohexene using bisphosphine ligands. The resulting cis-1-acetylamino-2-cyano-cyclopentane and -cyclohexane were obtained in high yields but only poor to moderate enantioselectivities.
Similarly, Lucarini et al., Chem. Asian J., 2010, 5, 550-554, report on diastereoselective syntheses of cis-4-phenyl-2-propionamido-tetraline via hydrogenation of racemic N-(4-phenyl-3,4-dihydronaphthalen-2-yl)propionamide which was catalyzed by rhodiumcomplexes including chiral phosphine ligands. However, only poor enantioselectivities could be achieved.
It is an object of the present invention to provide a process that is suitable for the enantioselective preparation of 1-substituted 2-aminotetraline and aminoindane derivatives as well as of 4-substituted 3-aminochromane, 3-aminothiochromane or 3-amino-1,2,3,4-tetrahydroquinoline derivatives. This process should be simple to carry out, based on selective reactions and suitable for the production on an industrial scale.
The object is achieved by the process described in detail below.